Modern cytogenetic techniques coupled with in vitro models of the allergic response permit an analysis of the genetic and environmental factors that affect immediate hypersensitivity. With the use of somatic cell hybrids and immunochemical, biochemical, and pharmacologic techniques, genetic linkage studies of IgE receptors, histamine production, storage, and release, and modulation of histamine release will be performed. Classical population genetics and developmental studies will also be employed. Quantitative studies of serum complement-mediated histamine release, particularly in genetic diseases of the complement system, will be performed and may contribute to an understanding not only of these diseases but some atopic conditions as well. The overall goal of these studies is to uncover some of the basic control mechanisms of allergic disease so that they may be described in molecular terms. Ultimately, these data may lead to a rational approach for the design of future therapeutic regimens.